POTS is a heterogeneous disorder of the autonomic nervous system that can result from multiple etiologies. An increased prevalence of vitamin B12, vitamin D 25-OH and iron deficiencies has been observed in patients with POTS. This study examined the prevalence of vitamin B1 deficiency and assessed response to vitamin B1 supplementation in the deficient POTS patients. Medical records of 65 consecutive patients with POTS evaluated at our clinic were reviewed. In this cohort (mean age 32, range 13-54 years; 89% female), 6% had vitamin B1 deficiency, and one of four deficient patients experienced significant improvement of POTS after oral vitamin B1 supplementation. A small subset of patients with POTS may have vitamin B1 deficiency. Testing for vitamin B1 deficiency and correcting the deficiency is recommended.

To explore whether hemocytometric measures could be qualified predictors for the effect of oral rehydration salts (ORS) in children with postural tachycardia syndrome (POTS). Thirty-five children with POTS and 29 healthy children were enrolled. General information, hemodynamic status, and baseline hemocytometric variables were collected. Children with POTS received ORS therapy and were followed up for 3 months. The independent risk factors of developing POTS were explored. A receiver-operating characteristic curve was used to evaluate predictive value of hemocytometric variables for therapeutic effectiveness of ORS therapy. Children with POTS had larger mean corpuscular volume (MCV) and lower mean corpuscular hemoglobin concentration (MCHC) values than controls (P < .05). The baseline MCV values positively correlated with heart rate elevation from supine to upright (r = 0.294, P < .05). Both larger MCV and lower MCHC values were independent risk factors of developing POTS (for MCV, P < .05, OR 1.222; for MCHC, P < .05, OR 0.936). In children with POTS, responders to ORS had baseline lower MCV and higher MCHC than nonresponders (P < .05). The receiver-operating characteristic curve for the predictive value of MCHC showed that area under the curve was 0.73. MCHC values could be used to predict the effectiveness of ORS for treating POTS in children.

To describe the development of a clinically and financially successful interdisciplinary pediatric pain rehabilitation program at a large tertiary academic medical center and present demographic and clinical information on the first 1000 patients. All patients who were consecutively admitted to this program between October 1, 2008, and March 31, 2015 were included in this review. The patients ranged in age from 9 to 24 years. The program is a 3-week, hospital-based outpatient treatment program that requires substantial parental involvement. At admission and discharge, patients completed the Center for Epidemiologic Studies of Depression Scale for Children, the Functional Disability Inventory, and the Pain Catastrophizing Scale for Children. Opioid use was also assessed. At admission, patients reported substantial pain-associated disability and depressive symptoms; they had elevated pain catastrophizing scores, and 16% were taking opioids. Primary sites/types of pain included head, abdomen, and generalized. Functional disability scores decreased significantly, from 27 to 9 after the program (<.001). Depression scale scores improved from 27 to 14 (<.001). Pain catastrophizing scores decreased significantly, from 26 to 14 (P<.001), at discharge from the program. All but 4 patients successfully tapered off of all opioid use by the conclusion of the program. Participation in a multidisciplinary pediatric pain rehabilitation program can be successful, with significant decreases in disability, depression symptoms, and pain catastrophizing, as well as discontinuation of opioid use.

Orthostatic intolerance is defined as the provocation of symptoms upon standing, commonly caused by neurogenic orthostatic hypotension (OH) and postural tachycardia syndrome (POTS), the etiology for which has not been fully uncovered yet. Many reports have described the occurrence of dysautonomia, orthostatic intolerance and POTS following febrile illness, presumably viral and post-vaccine. Furthermore, patients with dysautonomia have higher rates of autoimmune disorders such as Hashimoto thyroiditis and SLE. Recent evidence has shown the presence of adrenergic and cholinergic receptor antibodies in patients with POTS and orthostatic hypotension. In patients with cholinergic receptor antibodies, higher titers correlate with the disease severity. Few reports have shown that immunomodulation therapy resulted in significant improvement in symptoms. In this article, we review the available literature correlating autoimmunity with orthostatic intolerance syndromes. Future studies are warranted to evaluate the prevalence of such antibodies and examine different treatment modalities in this sub group of patients.

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

The human papillomavirus (HPV) vaccine is efficacious in preventing complications of human papillomavirus infection including cervical cancer. However, there have been case reports of adverse events occurring after vaccination, one being postural orthostatic tachycardia syndrome (POTS). This article reviews published data and other available information regarding the relationship between the human papillomavirus vaccine and POTS. Background information is provided regarding the human papillomavirus vaccine and the proposed post-vaccination adverse event POTS. Peer-reviewed literature, statements by government and medical advisory committees, and publicly available information published on this topic are examined. At this time, there is no conclusive evidence supporting a causal relationship between the human papillomavirus vaccine and POTS. Though a causal relationship has been postulated, it is of utmost importance to recognize that while temporal associations may be observed, conclusions of causality cannot be drawn from case reports and case series due to the small sample size and lack of control population.

Adolescents with cardiac diagnoses face unique challenges that can cause psychosocial distress. This study compares a Mindfulness-Based Stress Reduction (MBSR) program to a video online support group for adolescents with cardiac diagnoses. MBSR is a structured psycho-educational program which includes yoga, meditation, cognitive restructuring, and group support. A published feasibility study by our group showed significant reduction in anxiety following this intervention. Participants were randomized to MBSR or video online support group, and completed measures of anxiety, depression, illness-related stress, and coping pre- and post-6-session interventions. Qualitative data were obtained from post-intervention interviews. A total of 46 teens participated (mean 14.8 years; 63% female). Participants had congenital heart disease and/or cardiac device (52%), or postural orthostatic tachycardia syndrome (48%). Illness-related stress significantly decreased in both groups. Greater use of coping skills predicted lower levels of depression in both groups post-study completion. Higher baseline anxiety/depression scores predicted improved anxiety/depression scores in both groups. Each group reported the benefits of social support. The MBSR group further expressed benefits of learning specific techniques, strategies, and skills that they applied in real-life situations to relieve distress. Both the MBSR intervention and video support group were effective in reducing distress in this sample. Qualitative data elucidated the added benefits of using MBSR techniques to manage stress and symptoms. The video group format is useful for teens that cannot meet in person but can benefit from group support. Psychosocial interventions with stress management techniques and/or group support can reduce distress in adolescents with cardiac diagnoses.

Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is unexpectedly common and is associated with a high rate of gastrointestinal manifestations. We herein report the first documented case of mobile cecum associated with EDS-HT. A 21-year-old woman with repeated right lower abdominal pain was initially diagnosed with EDS-HT. Abdominal examinations performed in the supine position, such as CT and ultrasonography, showed no gross abnormalities. In contrast, oral barium gastrointestinal transit X-ray images obtained with changes in the patient's body position revealed position-dependent cecal volvulus with mobile cecum. She was finally discharged with a dramatic resolution of her symptoms after laparoscopic cecopexy for mobile cecum.

Human papillomavirus (HPV) vaccination prevents infections with HPV strains that cause certain cancers. Reports of postural orthostatic tachycardia syndrome (POTS) following HPV vaccination have raised safety concerns. We reviewed POTS reports submitted to the Vaccine Adverse Event Reporting System (VAERS). We searched the VAERS database for reports of POTS following any type of HPV vaccination (bivalent, quadrivalent, or nonavalent) from June 2006 to August 2015. We reviewed reports and applied established POTS diagnostic criteria. We calculated unadjusted POTS case reporting rates based on HPV vaccine doses distributed and conducted empirical Bayesian data mining to screen for disproportional reporting of POTS following HPV vaccination. Among 40,735 VAERS reports following HPV vaccination, we identified 29 POTS reports that fully met diagnostic criteria. Of these, 27 (93.1%) were in females and mean age was 14 years (range 12-32). Median time from vaccination to start of symptoms was 43 days (range 0-407); most (18, 75.0%) had onset between 0 and 90 days. Symptoms frequently reported concomitantly included headache (22, 75.9%) and dizziness (21, 72.4%). Twenty (68.9%) reports documented a history of pre-existing medical conditions, of which chronic fatigue (5, 17.2%), asthma (4, 13.8%), and chronic headache (3, 10.3%) were most common. Approximately one POTS case is reported for every 6.5 million HPV vaccine doses distributed in the United States. No empirical Bayesian data mining safety signals for POTS and HPV vaccination were detected. POTS is rarely reported following HPV vaccination. Our review did not detect any unusual or unexpected reporting patterns that would suggest a safety problem.

Ivabradine is a selective I  channel blocker that reduces heart rate without affecting other cardiovascular functions. In case reports and case series, it was shown to improve symptoms in patients with postural tachycardia syndrome (POTS). This retrospective study examined patients who were diagnosed with POTS and received ivabradine as part of their treatment. Forty-nine patients (47 females, 95.9%) received ivabradine. The average age was 35.1 ± 10.35 years. The most common symptoms were palpitations and lightheadedness and both improved significantly, 88.4% and 76.1% response rate, respectively. A total of 38 patients reported improvement in their symptoms. In addition, ivabradine resulted in an objective decrease in sitting and standing heart rate (78.1 ± 10.7 vs 72.5 ± 7.6, P-value: 0.01) and (107.4 ± 14.1 vs 95.1 ± 13.7, P-value: < 0.001), respectively, with no significant change in blood pressure. The most common reported side effect was luminous phenomena/visual brightness occurring in nine patients. However, none of the patients stopped ivabradine due to side effects. Our study shows that ivabradine is likely to be effective in treating patients with POTS. Nearly 78% of our cohort reported a significant improvement in symptoms with no major adverse effects reported. A future randomized, placebo-controlled trial is warranted.

Adolescents with postural orthostatic tachycardia syndrome (POTS) often have pain and functional impairment. This study evaluated how parental attributions of children's symptoms relate to child functional impairment. Adolescents with chronic pain and clinical symptoms suggestive of autonomic dysfunction (fatigue, dizziness, nausea) that attended a multidisciplinary chronic pain clinic completed measures of depression, anxiety, and functioning (n = 141). Parents of 114 of these patients completed the Parent Pain Attribution Questionnaire (PPAQ), a measure indicating the extent they believe physical and psychosocial factors account for their child's health condition. Patients were retrospectively grouped as to whether or not they had significant POTS on tilt table testing (n = 37). Greater parental attribution to physical causes was associated with increased levels of functional disability whether patients had POTS ( r = 0.45, P = .006) or not ( r = 0.25, P = .03). These results suggest that providers should advocate a more comprehensive family-oriented rehabilitative approach to treatment.

Presyncope and syncope are common medical findings, with a > 40% estimated lifetime prevalence. These conditions are often elicited by postural stress and can be recurrent and accompanied by debilitating symptoms of cerebral hypoperfusion. Therefore, it is critical for physicians to become familiar with the diagnosis and treatment of common underlying causes of presyncope and syncope. In some patients, altered postural hemodynamic responses result from a failure of compensatory autonomic nervous system reflex mechanisms. The most common presentations of presyncope and syncope secondary to this autonomic dysfunction include vasovagal syncope, neurogenic orthostatic hypotension, and postural tachycardia syndrome. The most sensitive method for diagnosis is a detailed initial evaluation with medical history, physical examination, and resting electrocardiogram to rule out cardiac syncope. Physical examination should include measurement of supine and standing blood pressure and heart rate to identify the pattern of hemodynamic regulation during orthostatic stress. Additional testing may be required in patients without a clear diagnosis after the initial evaluation. Management of patients should focus on improving symptoms and functional status and not targeting arbitrary hemodynamic values. An individualized structured and stepwise approach should be taken for treatment, starting with patient education, lifestyle modifications, and use of physical counter-pressure manoeuvres and devices to improve venous return. Pharmacologic interventions should be added only when conservative approaches are insufficient to improve symptoms. There are no gold standard approaches for pharmacologic treatment in these conditions, with medications often used off label and with limited long-term data for effectiveness.

To determine the value of salivary cortisol concentrations in predicting the efficacy of sleep-promoting treatment in children with postural tachycardia syndrome (POTS). This prospective study involved 40 children with POTS and 20 healthy children (controls). POTS was diagnosed using the head-up or head-up tilt test. Patients with POTS received a sleep-promoting treatment: >8 hours of sleep every night and a midday nap in an appropriate environment; no drinking water or exercising before bedtime; and urination before bedtime. The Pittsburgh Sleep Quality Index was used to evaluate sleep quality, and symptom scores were used to assess POTS severity. Salivary samples were collected upon awakening, 30 minutes after awakening, at 12:00 p.m., 4:00 p.m., and 8:00 p.m., and at bedtime before treatment. Enzyme-linked immunosorbent assay was used to measure salivary cortisol concentrations. Cortisol concentrations were significantly higher in patients with POTS than in the controls at all time points (P < .05 for all). PSQI scores were significantly higher in patients with POTS (7.2 ± 3.0) than in the controls (1.35 ± 1.39; t = -10.370, P <.001). Salivary cortisol concentrations at awakening were significantly higher in responders than in nonresponders (4.83 ± 0.73 vs 4.05 ± 0.79 ng/mL, t = -3.197, P = .003). The area under the receiver operating characteristic curve was 75.8%, (95% CI 59.3%-92%). Cut-off at-awakening salivary cortisol concentrations of >4.1 ng/mL yielded 83.3% sensitivity and 68.7% specificity in predicting therapeutic efficacy. At-awakening salivary cortisol concentrations may predict the efficacy of sleep-promoting treatment in patients with POTS.

It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS. Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year. Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls). While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role.

This study was designed to analyse the serum resistin level in children with postural tachycardia syndrome (POTS) and its clinical significance. Twenty-one children with POTS and 31 healthy children as controls participated in the study. Clinical characteristics, heart rate and blood pressure in the supine and upright positions were monitored and collected during an upright test, and the symptom scoring of POTS patients was recorded. The serum resistin levels of patients in both groups were determined by enzyme-linked immunosorbent assay. The change in serum resistin levels in the POTS group before and after standing, as well as its correlation with symptom scores and change in heart rate after standing, was analysed. Compared with the control group, the serum resistin levels in the POTS group were significantly increased (P < 0.01). The serum resistin levels in the POTS group before and after standing did not differ (P > 0.05). There was a negative correlation between the serum resistin levels and a change in heart rate from the supine to upright position (correlation coefficient = -0.615, P < 0.01). Moreover, serum resistin levels were negatively correlated with symptom scores (correlation coefficient = -0.493, P < 0.05). Serum resistin levels in children with POTS were significantly higher than those in healthy children and negatively correlated with a change in heart rate from the supine to upright position and symptom scores. These results suggest a protective role of increased resistin in the pathogenesis of POTS.

Intravenous immunoglobulin therapy is FDA approved for the immune-mediated peripheral nerve disorders Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. Immunoglobulin therapy has been used increasingly with significant efficacy in the treatment of patients with disabling autoimmune forms of dysautonomia, which are most often small fiber (autonomic and/or sensory) polyneuropathies. It is recognized by most who treat these disorders, however, that patients with autonomic dysfunction treated with intravenous immunoglobulin therapy develop aseptic meningitis or severe lingering headache more frequently than other patient populations when this therapy is dosed in the traditional fashion. We discuss our combined 27 years of experience with the use of immunoglobulin and other immune modulatory therapy in patients with autoimmune small fiber polyneuropathy.

The study was designed to evaluate the changes of plasma homocysteine (Hcy) level in children with postural tachycardia syndrome (POTS) and explore its significance. A total of 65 subjects were recruited in our study, of whom 35 children were in the POTS group and 30 healthy children were in the control group. Plasma Hcy levels were determined in all subjects. The relationship between the plasma Hcy level and the symptom score was analyzed in the 35 POTS patients. The relationship between the plasma Hcy level and the change in heart rate from the supine to upright position (ΔHR) and between the plasma Hcy level and the rate of increase in heart rate from the supine to upright position (ΔHR/sHR × 100%) were analyzed in all subjects. The plasma Hcy levels were significantly higher in the children with POTS than those in the control group (9.78 [7.68, 15.31] μmol/L vs. 7.79 [7.46, 9.63] μmol/L, < 0.05). The plasma Hcy levels were positively correlated with symptom scores in the POTS patients ( = 35, = 0.522, < 0.01). The plasma Hcy levels were also positively correlated with ΔHR ( = 65, = 0.332, < 0.01) and ΔHR/sHR × 100% ( = 65, = 0.341, < 0.01) in all the subjects. In conclusion, the plasma Hcy levels were elevated in the children with POTS positively correlated with the severity of POTS, suggesting that Hcy might be involved in the pathogenesis of POTS.

Orthostatic intolerance is common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In some ME/CFS case definitions, orthostatic intolerance is considered a core feature of the disorder. Some studies have employed tilt table tests lasting 2-5 min to diagnose one common form of orthostatic intolerance, postural tachycardia syndrome (POTS). We examined the diagnostic yield of abbreviated durations of tilt testing in adults meeting criteria for ME/CFS, and identified the proportion with POTS misdiagnosed using testing of <10 min. Eligible participants were consecutive individuals satisfying study criteria for ME/CFS and POTS evaluated at the Stichting CardioZorg (SCZ, Hoofddorp, NL) between November 2012 and August 2018. Individuals being treated with medications commonly used to manage orthostatic intolerance were excluded. Head-up tilt table testing involved 15 min of supine posture then 20 min at 70 degrees upright. Only the data from the first 10-min upright were used. POTS was defined as an increase in HR during a maximum of 10 min of upright tilt of at least 30 beats per minute (bpm), in the absence of either classical or delayed orthostatic hypotension. We measured the time until HR criteria for POTS were reached using survival curves, and compared survival curves between subgroups divided by age, sex, disease duration, and degree of hypocapnia during the test. Of 627 individuals with ME/CFS evaluated during the study period, 155 met criteria for POTS. The median time to reaching HR criteria for POTS was 3 min. A two-minute tilt table test would miss 55% (95% CI, 48-63%) of those meeting POTS criteria over the course of 10 min upright. The median time to reaching HR criteria for POTS did not differ by sex, age, duration of ME/CFS, or hypocapnia during tilt. Abbreviated tilt table testing misses a substantial proportion of those ultimately diagnosed with POTS during a 10-min tilt table test, and should be abandoned for the clinical diagnosis and in epidemiologic studies designed to estimate the prevalence of POTS among those with ME/CFS.

To explore the predictive value of immediate heart rate alteration from supine to upright in the differential diagnosis between vasovagal syncope (VVS) and postural tachycardia syndrome (POTS) in children. A total of 76 pediatric outpatients or inpatients who visited the Peking University First Hospital from July 2016 to November 2017 were recruited in the study. Among them, 52 patients were diagnosed with VVS and 24 patients were diagnosed with POTS. The differential diagnostic value of acceleration index (AI) and 30/15 ratio was evaluated by the receiver operating characteristic (ROC) curve. An external validation test was performed in another 46 patients. Compared with the cases in the VVS group, patients in the POTS group had a significantly increased AI but a decreased 30/15 ratio (33.495 ± 8.472 vs. 23.440 ± 8.693, < 0.001; 0.962 ± 0.067 vs. 1.025 ± 0.084, = 0.002; respectively). The ROC curves showed that AI and 30/15 ratio were useful for differentiating POTS from VVS. A cut-off value of AI set at 28.180 yielded a sensitivity of 79.2% and a specificity of 73.1%. A cut-off value of 30/15 ratio set at 1.025 yielded a sensitivity of 87.5% and a specificity of 61.5%. A combined use of these two indices improved the sensitivity to 95.8% when either AI or 30/15 was used, and specificity to 80.8% with the use of both AI and 30/15 at the same diagnosis. The external validation test showed that the positive and negative predictive values of the AI and 30/15 ratio were 77.3 and 79.2%, and 72.0 and 81.0%, respectively. The positive predictive value increased to 87.5% when both the AI and 30/15 ratio cut-off values were used together. The AI and 30/15 ratio, which are easy to perform and non-invasive, have proper sensitivity and specificity to differentiate patients with POTS from those with VVS. The combination of these two indices significantly improves the predictive value.

One third of Gulf War Illness (GWI) subjects in a recent study were found to develop transient postural tachycardia after submaximal exercise stress tests. Post-exercise postural tachycardia is a previously undescribed physiological finding. A new GWI cohort was studied to verify this novel finding and characterize this cardiovascular phenomenon. Subjects followed the same protocol as before. The change in heart rate between recumbent and standing postures (ΔHR) was measured before exercise, and after submaximal bicycle exercise. About one-fourth of the verification cohort (14/57) developed transient postural tachycardia after submaximal exercise. These subjects were the Stress Test Activated Reversible Tachycardia (START) phenotype. The largest change was observed between pre-exercise and time points 2 ± 1 (mean ± SD) hours post exercise (1 Peak Effect). Eleven subjects had Postural Tachycardia Syndrome (POTS) before and after exercise. The remaining subjects had normal ΔHR (12 ± 5 bpm) and no 1 Peak Effect, and were the Stress Test Originated Phantom Perception phenotype (STOPP). These findings indicate that about one-fourth of all Gulf War Illness study participants (24/90) developed transient postural tachycardia after the submaximal exercise stress test. The START phenotype was defined as being distinctly different from POTS. Additional studies are required to examine this phenomenon in other illnesses and to determine pathological mechanisms.

A 36-year-old female with symptoms of orthostatic intolerance and syncope was diagnosed with vasovagal syncope on a tilt table test and with postural tachycardia syndrome (POTS) after a repeat tilt table test. However, an echocardiogram at our institution revealed obstructive cardiomyopathy without severe septal hypertrophy, with a striking increase in left ventricular outflow tract gradient from 7 mmHg at rest to 75 mmHg during Valsalva, with a septal thickness of only 1.3 cm. Cardiac MRI showed an apically displaced multiheaded posteromedial papillary muscle with suggestion of aberrant chordal attachments to the anterior mitral leaflet contributing to systolic anterior motion of the mitral valve. She underwent surgery with reorientation of the posterior medial papillary muscle head, resection of the tethering secondary chordae to the A1 segment of the mitral valve, chordal shortening and tacking of the chordae to the A1 and A2 segments of the mitral valve, and gentle septal myectomy. After surgery, she had significant improvement in her prior symptoms. To our knowledge, this is the first reported case of obstructive cardiomyopathy without severe septal hypertrophy with abnormalities in papillary muscle and chordal attachment, in a patient diagnosed with vasovagal syncope and POTS.

Postural tachycardia syndrome (POTS) is the combination of an exaggerated heart rate response to standing, in association with symptoms of lightheadedness or pre-syncope that improve when recumbent. The condition is often associated with fatigue and brain fog, resulting in significant disruptions at a critical time of diagnosis in adolescence and young adulthood. The heterogeneity of the underlying pathophysiology and the variable response to therapeutic interventions make management of this condition challenging for both patients and physicians alike. Here, we aim to review the factors and mechanisms that may contribute to the symptoms and signs of POTS and to present our perspectives on the clinical approach toward the diagnosis and management of this complex syndrome.

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management.

In the last decade, a group of chronic disorders associated with fatigue (CDAF) emerged as the leading cause of chronic fatigue, chronic pain, and functional impairment, all of which have been often labeled in clinical practice as chronic fatigue syndrome (CFS) or fibromyalgia. While these chronic disorders arise from various pathophysiologic mechanisms, a shared autoimmune or immune-mediated etiology could shift the focus from symptomatic treatment of fatigue and pain to targeted immunomodulatory and biological therapy. A clinical paradigm shift is necessary to reevaluate CFS and fibromyalgia diagnoses and its relationship to the CDAF entities, which would ultimately lead to a change in diagnostic and therapeutic algorithm for patients with chronic fatigue and chronic pain. Rather than uniformly apply the diagnoses of CFS or fibromyalgia to any patient presenting with unexplained chronic fatigue or chronic pain, it may be more beneficial and therapeutically effective to stratify these patients into more specific diagnoses in the CDAF group.

The aim of this study was to investigate the association of autonomic nervous system abnormalities on head-up tilt table test (HUTT) with generalized joint hypermobility, expressed by Beighton score (BS). This was a prospective study that included 115 consecutive patients (91 females; mean age 34.35 ± 14.11) referred either for the HUTT or testing of the cardiovascular autonomic reflexes together with HUTT. Generalized joint hypermobility was evaluated according to the BS system after which HUTT was performed. Clinically significant BS was considered if ≥4. Fifteen patients (15.1%) had BS ≥4. Results of the HUTT were normal in 58 (50.4%) patients and in 57 (49.6%) patient HUTT was abnormal. Fifteen (13.0%) patients fulfilled criteria for orthostatic hypotension, 30 (26.1%) for reflex syncope and 21 (18.3%) for postural orthostatic tachycardia syndrome. Patients with pathological findings on HUTT had significantly higher BS compared to patients with normal HUTT (median 1 vs. 0, p = 0.001). There was a significant association between participants with BS ≥4 and pathological HUTT (χ[1] = 6.392, p = 0.011). Results of the multivariate regression analysis revealed that increase in the BS is associated with the increased likelihood of HUTT pathology (Exp[B] 1.44, 95% CI 1.084-1.922, p = 0.012), while increase in age is associated with lower risk of HUTT pathology (Exp[B] 0.968, 95% CI 0.939-0.998, p = 0.036). There is an association between autonomic nervous system abnormalities on HUTT test and generalized joint hypermobility.